Microarray analysis of miRNAs during hindgut development in rat embryos with ethylenethiourea‑induced anorectal malformations.
Microarray analysis of miRNAs during hindgut development in rat embryos with ethylenethiourea‑induced anorectal malformations.
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亚乙基硫脲诱导的肛门直肠畸形大鼠胚胎后肠发育过程中 miRNA 的微阵列分析
DOI：
10.3892/ijmm.2018.3809
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发表时间：
2018-11
影响因子：
5.4
通讯作者：
Bai YZ
中科院分区：
文献类型：
--
作者：
Long CY;Tang XB;Wang WL;Yuan ZW;Bai YZ
肛门直肠畸形（ARMs）是最常见的先天性消化道畸形之一，然而，这种疾病的发病机制仍有待充分阐明。microRNAs（miRNAs）在胃肠道发育中起重要作用，可能参与ARMs的发病机制。本研究的目的是分析miRNAs的表达谱，并研究其在乙烯硫醚（ETU）诱导的ARMs大鼠中的潜在功能。Wistar孕鼠36只，随机分为对照组和ETU治疗组。ETU治疗组于妊娠第10天（GD10）灌胃1%ETU（125 mg/kg），对照组给予相应剂量的生理盐水。在GD 14、GD 15和GD 16通过剖宫产收获胚胎。从胎儿中分离后肠组织用于RNA提取和微阵列分析，然后进行生物信息学分析和逆转录-定量聚合酶链反应（RT-qPCR）验证。总体而言，与正常组相比，ARM组在GD14、GD15和GD16分别有38、49和42种miRNA差异表达（均上调）。前18个miRNAs，|log2（倍数变化）|> 4.25个进行进一步的生物信息学分析。在这些miRNAs中，5个在两个时间点差异表达，并参与ARM相关的信号通路。RT-qPCR结果显示，与正常对照组相比，ARMs大鼠中有3种miRNA（miR-125b-2 - 3p、miR-92a-2 - 5p和miR-99a-5p）的表达差异显著。结果提示，大鼠肛门直肠形成关键时间点miR-125 b-2 - 3p、miR-92 a-2 - 5p和miR-99 a-5p的差异表达可能在ARM的发病机制中发挥作用。
Anorectal malformations (ARMs) are one of the most common congenital malformations of the digestive tract; however, the pathogenesis of this disease remains to be fully elucidated. MicroRNAs (miRNAs) are important in gastrointestinal development and may be involved in the pathogenesis of ARMs. The present study aimed to profile miRNAs and examine their potential functions in rats with ethylenethiourea (ETU)-induced ARMs. Pregnant Wistar rats (n=36) were divided randomly into ETU-treated and control groups. The rats in the ETU-treated group were gavage-fed 1% ETU (125 mg/kg) on gestational day 10 (GD10), whereas the control group rats received a corresponding dose of saline. Embryos were harvested by cesarean section on GD14, GD15 and GD16. Hindgut tissue was isolated from the fetuses for RNA extraction and microarray analysis, followed by bioinformatics analysis and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) validation. Overall, 38 miRNAs were differentially expressed (all upregulated) on GD14, 49 (32 upregulated and 17 downregulated) on GD15, and 42 (all upregulated) on GD16 in the ARM group compared with the normal group. The top 18 miRNAs with |log2(fold change)| >4.25 were selected for further bioinformatics analysis. Among these miRNAs, five were differentially expressed at two time-points and were involved in ARM-associated signaling pathways. The RT-qPCR analysis revealed that three miRNA (miR), miR-125b-2-3p, miR-92a-2-5p and miR-99a-5p, were significantly differentially expressed in rats with ARMs compared with the normal group. In conclusion, the results suggested that the differential expression of miR-125b-2-3p, miR-92a-2-5p and miR-99a-5p during key time-points of anorectal formation in rats may have functions in the pathogenesis of ARM.
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影响因子：
12.4
作者：
通讯作者：
--
DOI：
10.1002/ajmg.1532
发表时间：
2001-10-15
期刊：
AMERICAN JOURNAL OF MEDICAL GENETICS
影响因子：
--
作者：
Cuschieri, A
通讯作者：
Cuschieri, A
影响因子：
5.4
作者：
Draaken, Markus;Prins, Wiebke;Ludwig, Michael
通讯作者：
Ludwig, Michael
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DOI：
10.1002/bdra.20576
发表时间：
2009-07-01
影响因子：
--
作者：
Guan, Kaoping;Li, Hui;Yuan, Zhengwei
通讯作者：
Yuan, Zhengwei
影响因子：
2.4
作者：
Bai, YZ;Chen, H;Wang, WL
通讯作者：
Wang, WL